Critically evaluate the interpretation of plasma troponin measurement in critically ill patients.
• Troponin I, T and C form a 3 unit complex with tropomyosin in cardiac actin filament, CTnI and cTnT used as cardiac specific markers, small amount in cytoplasm but a large actin pool, slowly released, and slowly degraded with small elevation in renal failure
• Greater sensitivity to cardiac damage than CK-MB which can also be found in skeletal muscle (increased in myopathies), gut, uterus, and IgG complexes CK-MB, rises 4-6 h after onset symptoms for myocardial infarction, useful prognostic marker in acute coronary syndromes (higher level = worse prognosis)
• Elevated level also seen with PE, sepsis, myocarditis, pericarditis, cardiac trauma, drug- induced myocardial injury, cardioversion
This question is almost identical to Question 10 from the second paper of 2011.
Rationale for the use of troponin in the critically ill:
- Troponin is an enzyme involved in the excitation-contraction coupling of the myocardium.
- Troponin T serves to attach the troponin complex to actin and tropomyosin.
- Myocardiac damage (for example infarction) causes the release of troponin.
- There is a cytosolic pool (which is released early in the infarct) and a structural pool (which is slowly released over days as the damaged myocardium decomposes).
Advantages of using troponin in critically ill patients
- Its a sensitive and specific marker of myocardial ischaemia.
- It is more sensitive and specific than AST, CK and CK-MB (which are also found is skeletal muscle)
- It is an independent predictor of 30-day mortality in STEMI
- It is associated with a poorer outcome in the critically ill patients.
- Troponin levels can be used to monitor for myocardial ischaemia in critically ill patients when history and examination are unreliable.
Advantages of using troponin in acute coronary syndromes
- Troponin forms a part of the ECS and AHA universal definition of acute coronary syndrome (it consists of a troponin rise as well as a demonstration of ischaemic symptoms, echocardiographic evidence, or ECG changes.)
- The troponin levels are not diagnostic, but are a risk stratification tool to be used together with echocardiography, ECG, history and examination.
- Troponin levels can be used for the late diagnosis of MI and to monitor for reinfarction
- The use of troponin as a part of a risk stratification strategy is important in selecting patients for anticoagulation and anti-platelet therapy, so as to prevent the exposure of patients to unnecessary bleeding risk.
Disadvantages for the use of troponin in critical illness
- A reliance on biomarkers may become unhealthy if it takes focus off clinical examination and history.
- It is not quantitatively validated outside the setting of ACS / AMI, but only qualitatively: i.e. a "positive" troponin is associated with worse outcomes in noncardiac critical illness, but we don't know whether a higher troponin is associated with a proportionally higher mortality.
- As with all biomarkers, inappropriately low threshold levels or testing out of appropriate clinical context could give rise to unnecessary treatments (eg. loading doses of antiplatelet drugs) or investigations (eg. angiography, with needless contrast exposure)
- Troponin levels can be raised for a variety of non-cardiac reasons.In their 2006 article, Korff et aloffer an excellent table of things which cause troponin elevation, together with the mechanism of troponin release or assay confusion. Their Table 1 is reinterpreted here.
- Renal failure - its cleared renally
- Atrial fibrillation
- Cardiac trauma
- Pulmonary embolism
- Acute stroke
- Intracranial haemorrhage
- Severe burns
- Rhabdomyolysis (particularly during recovery)
- Skeletal muscle damage in glycogen storage disease
- Defective assay (cross-reactivity with skeletal troponin isoforms)
This article has a nice graph of cardiac biomarker concentrations over time after an infarct:
Wu et al; National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases. Clinical Chemistry 45:7 1104 –1121 (1999)
There is a CICM fellowship question regarding the critical appraisal of troponin in the ICU population.
The ECS and AHA statement referred to in the college answer is this article published in Circulation in 2007:
(Kristian Thygesen et al; Universal Definition of Myocardial Infarction. Circulation 2007, 116:2634-2653
This article from Current Opinion in Critical care (2004) discusses the various causes of raised troponin among ICU patients:
Ammann et al,Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. Journal of the American College of Cardiology Volume 41, Issue 11, 4 June 2003, Pages 2004–2009
The fact that troponin rise among the critically ill population is associated with a poorer prognosis is supported by this study:
Gunnewiek et al. Cardiac troponin elevations among critically ill patients. Current Opinion in Critical Care: October 2004 - Volume 10 - Issue 5 - pp 342-346
Liu, Michael, et al. "Prognostic Value of Initial Elevation in Cardiac Troponin I Level in Critically Ill Patients Without Acute Coronary Syndrome." Critical care nurse 35.2 (2015): e1-e10.
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Ammann, P., et al. "Elevation of troponin I in sepsis and septic shock." Intensive care medicine 27.6 (2001): 965-969.
Landesberg, Giora, et al. "Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation." Critical care medicine 42.4 (2014): 790-800.
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Tiruvoipati, Ravindranath, Nasreen Sultana, and David Lewis. "Cardiac troponin I does not independently predict mortality in critically ill patients with severe sepsis." Emergency Medicine Australasia 24.2 (2012): 151-158.
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Vieillard-Baron, Antoine, et al. "Actual incidence of global left ventricular hypokinesia in adult septic shock." Critical care medicine 36.6 (2008): 1701-1706.
Donzé, Jacques D., et al. "Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study." BMJ 349 (2014): g5334.
Korff, Susanne, Hugo A. Katus, and Evangelos Giannitsis. "Differential diagnosis of elevated troponins." Heart 92.7 (2006): 987-993.
Wens, Stephan CA, et al. "Elevated Plasma Cardiac Troponin T Levels due to Skeletal Muscle Damage in Pompe Disease." Circulation: Genomic and Precision Medicine (2016): CIRCGENETICS-115.
Sribhen, Kosit, Rewat Phankingthongkum, and Nilrat Wannasilp. "Skeletal muscle disease as noncardiac cause of cardiac troponin T elevation." Journal of the American College of Cardiology 59.14 (2012): 1334-1335.